- Email: [email protected]
Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung
Early Results of a Prospective Study of Limited Resection for Bronchioloalveolar Adenocarcinoma of the Lung Yasushi Yamato, MD, Masanori Tsuchida, MD, Takehiro Watanabe, MD, Tadashi Aoki, MD, Naoya Koizumi, MD, Hajime Umezu, MD, and Jun-ichi Hayashi, MD Departments of Thoracic and Cardiovascular Surgery, Radiology, and Surgical Pathology, Niigata University School of Medicine, Niigata, Japan
Background. We reported that bronchioloalveolar adenocarcinoma (BAC) without active fibroblastic proliferation of the lung had no lymph node and pulmonary metastasis and had a favorable prognosis. However, there has been no prospective trial regarding limited pulmonary resection for this type of BAC. The purpose of this study is to confirm the effectiveness of limited resection for histologically confirmed BAC without active fibroblastic proliferation. Methods. From 1996 through 1999, 42 patients who had small peripheral lung tumors (⬉ 20 mm), suspected of being BAC, were enrolled in this trial. The patient population consisted of 24 men and 18 women with a mean age of 58.4 years. Limited resection was completed when BAC, without both active fibroblastic proliferation and lymph node metastasis, was con-
firmed histologically by intraoperative pathologic examination. Results. Limited resection was completed in 36 patients, wedge resection in 34, and segmentectomy in 2 patients. In 6 patients, the procedure was converted into lobectomy because of pathologic invasive sign in 3, active fibroblastic proliferation in 1, and for other reasons in 2 patients. All patients have been followed for a median follow-up period of 30 months and are alive without sign of recurrence. Conclusions. Our early results indicate that limited resection may be an acceptable alternative to lobectomy for histologically confirmed BAC without active fibroblastic proliferation. (Ann Thorac Surg 2001;71:971– 4) © 2001 by The Society of Thoracic Surgeons
I
attention on this point and reviewed 28 patients with BAC with minimal fibrotic foci who underwent lobectomy and systemic lymph node dissection. All of the patients had neither lymph node nor pulmonary metastasis with favorable prognoses [10]. On the basis of these promising results, we performed a prospective study to confirm the effectiveness of limited resection for histologically confirmed BAC without active fibroblastic proliferation.
n recent years in Japan, small peripheral adenocarcinomas of the lung have become more commonly detected by computed tomography (CT) [1, 2]. However, limited pulmonary resection for small peripheral adenocarcinomas remains controversial [3, 4], because it is known that 10% to 20% of small adenocarcinomas of the lung have lymph node involvement or pulmonary metastasis [5–7]. Shimosato and colleagues [8] have demonstrated that the characteristics of the central fibrosis (scar) were probably more important than the size of tumor for estimating the prognosis of patients with peripheral adenocarcinoma of the lung. Noguchi and colleagues [9] grouped small adenocarcinomas of the lung into six types by histologic examination and have reported that type A (localized bronchioloalveolar carcinoma [BAC]) and type B (localized BAC with foci of structural collapse of alveoli) showed the most favorable prognosis of the six types, whereas type C (localized BAC with foci of active fibroblastic proliferation) was thought to be an advanced stage of types A and B. We focused our
Accepted for publication Oct 18, 2000. Address reprint requests to Dr Yamato, Department of Thoracic and Cardiovascular Surgery, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata City, 951-8510 Japan; e-mail: [email protected].
© 2001 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
Material and Methods From October 1996 through August 1999, 42 patients who had small peripheral (situated peripherally beyond subsegmental bronchi) lung tumors of 2 cm or less and were suspected of BAC based on chest CT and by CT-guided lung biopsy were enrolled in a single center trial. Chest CT demonstrated no lymph node metastases, and routine examination revealed no metastatic lesions. The patient population consisted of 24 men and 18 women, with a mean age of 58.4 years (range, 32 to 76 years) at the time of the pulmonary resection. In 39 of the 42 patients, diagnosis of BAC was established preoperatively by CT-guided lung biopsy. Radiologically, this type of BAC is expressed by CT as a clearly demarcated nodular area 0003-4975/01/$20.00 PII S0003-4975(00)02507-8
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YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
Ann Thorac Surg 2001;71:971– 4
Fig 1. High resolution computed tomography showing a clearly demarcated nodular area of lower density than vessels, so-called ground-glass attenuation.
of lower density than vessels, the so-called ground-glass attenuation (Fig 1) [11]. The tumor diameters measured by chest CT ranged from 6 to 20 mm, with a mean diameter of 13.6 mm. Table 1 summarized the clinical characteristics of these patients. Histopathologically, this type of BAC shows retained alveolar structure and replacement growth pattern of alveolar epithelial cells without active fibroblastic proliferation and invasive sign to the pleura and stroma (Fig 2), which almost corresponds to Noguchi’s classification type A or B [9]. Intraoperative pathologic examination was done using hematoxylin and eosin-stained section from the largest cut surface of the tumor. Postoperative pathologic examinaTable 1. Characteristics of 42 Patients Enrolled in This Study Characteristics
Data
Age (yr) Sex Male Female Preoperative diagnosis Adenocarcinoma Undiagnosed Tumor diameter (mm) measured by Chest CT Resected specimen Surgical procedures Wedge resection Segmental resection Lobectomy Reasons for conversion to lobectomy Pathological invasive sign AFP Multiple lesions in one lobe Nonpalpable lesion
32–76 (58.4) 24 18 39 3 6 –20 (13.6) 4 –25 (12.3) 34 2 6 3 1 1 1
Data are given as range (mean) or number. CT ⫽ computed tomography;
Fig 2. Microscopic findings of bronchioloalveolar adenocarcinoma without active fibroblastic proliferation showing retained alveolar structure and replacement growth pattern of alveolar epithelial cells without active fibroblastic proliferation. (Hematoxylin and eosin stain; A: original magnification, ⫻2; B: original magnification, ⫻160.)
AFP ⫽ active fibroblastic proliferation.
tion was performed using hematoxylin and eosin and elastica van Gieson-stained sections from two or three cut surfaces of the tumor. Wedge resection or segmental resection with hilar and mediastinal lymph nodes sampling (two or three nodes in almost all patients) was performed on these patients through a thoracotomy, followed by intraoperative pathologic examination in all patients. After BAC without both active fibroblastic proliferation and invasive signs with no lymph node metastasis was confirmed histologically, limited resection was completed. If active fibroblastic proliferation, invasive sign, or lymph node metastasis was detected by intraoperative pathologic examination, the surgical procedure was converted into a lobectomy with lymph node dissection (Fig 3). Informed consent was obtained from all patients. Only 1 patient of those who were thought to be eligible for limited resection refused to participate in this study. Patients enrolled in this study have been followed at 3-month intervals after operation. Follow-up evalua-
Ann Thorac Surg 2001;71:971– 4
YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
973
Comment
Fig 3. The study design of limited resection for bronchioloalveolar adenocarcinoma (BAC). (AFP ⫽ active fibroblastic proliferation; CT ⫽ computed tomography.)
tion included blood examination and chest roentgenogram at 3-month intervals, and chest CT at 6-month intervals. The follow-up periods have ranged from 47 to 12 months: 12 to 23 months in 12 patients, 24 to 35 months in 20, and 36 to 47 months in 10 patients. The median follow-up period was 30 months.
Results There were no operative or hospital deaths and no serious complications postoperatively. Limited resection was completed in 36 patients, wedge resection in 34, and segmental resection in 2 patients. In 6 patients, the surgical procedure was converted into lobectomy because of pathologic invasive sign in 3 patients, active fibroblastic proliferation in 1, multiple lesions in one lobe in 1, and nonpalpable lesion in 1 patient. In all patients, there was no metastasis in hilar and mediastinal lymph nodes that were sampled intraoperatively. Postoperative pathologic diagnoses of all tumors were in accord with intraoperative pathologic results. The tumor diameter measured in resected specimens ranged from 4 to 25 mm, with a mean diameter of 12.3 mm. To localize nonpalpable peripheral pulmonary lesions, we have developed a new technique of CT-guided agar marking [12]. Agar was injected through an 18-gauge needle and placed near the target lesion with CT. Agar could be detected as a hard nodule by manual palpation, and the lesion was resected during thoracotomy. Sixteen of the 42 patients required agar marking preoperatively to localize and resect nonpalpable tumors. All patients have been followed to date and are alive without a sign of local or distant recurrence.
In recent years, small peripheral adenocarcinomas of the lung have been more commonly detected in Japan as a result of recent advances in diagnostic radiology and lung cancer screening programs using chest CT [1, 2]. Even for these small tumors, lobectomy with lymph node dissection is commonly performed in Japan, because it is known that 10% to 20% of small peripheral adenocarcinomas of the lung constitutes progressive disease. Takizawa and colleagues [5] demonstrated that 17% of small (⬍ 2 cm) peripheral adenocarcinomas had lymph node metastases and concluded that lobectomy and hilar/mediastinal lymphadenectomy are required even in such cases. Konaka and colleagues [6] similarly analyzed patients with peripheral lung cancers of 2.0 cm or less in diameter having undergone surgical resection and demonstrated that 17.5% of all patients had lymph node involvement. For these reasons, the indication of limited pulmonary resection for small peripheral adenocarcinomas remains controversial and has not been clearly established. There have been several studies concerning limited resection for small peripheral lung cancer. The Lung Cancer Study Group (Ginsberg and Rubinstein) [3] reported a prospective randomized trial comparing limited resection with lobectomy for patients with peripheral T1N0 non-small cell lung cancer and concluded that lobectomy must still be considered the surgical procedure of choice for patients with these tumors. On the other hand, Warren and Faber [13] reviewed, retrospectively, patients with stage I non-small cell lung cancer having undergone either segmental resection or lobectomy and the results revealed that there was a very high loco/regional recurrence rate in the segmentectomy group, however, no significant difference in survival rates between patients with tumors 3.0 cm or smaller in diameter undergoing lobectomy and patients undergoing segmentectomy. Considering the results of these studies, we believe that it is not only the size but also the histologic characteristics of tumors that need to be considered to determine the indication of limited resection for small peripheral lung cancers. However, reports documenting the indication of limited pulmonary resection for small peripheral lung cancers also taking into account the histologic type have been scarce. Shimosato and colleagues [8] reexamined peripheral lung cancers of less than 3 cm in diameter histologically and stated that the degree of collagenization or hyalinization might indicate the relative length of time between the tumor development and its surgical removal. They revealed that in adenocarcinoma with increased collagenization or hyalinization in the fibrotic focus, the degree of pleural invasion and incidence of lymph node metastasis and blood vessel invasion were greater and thus the prognosis of the patient was poorer than in cases with no or slight collagenization, and concluded that the characteristics of the central fibrosis (scar) were probably more important than tumor size for estimating the prognosis of patients with peripheral adenocarcinoma of less than 3 cm in diameter. Noguchi and colleagues [9] have
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YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
reported that they grouped small adenocarcinomas of the lung into six types by histologic examination, and type A (localized BAC) and type B (localized BAC with foci of structural collapse of alveoli) showed no lymph node metastasis, rare vascular and pleural invasion, and the most favorable prognosis (100% 5-year survival) of the six types, whereas type C (localized BAC with foci of active fibroblastic proliferation) showed a less favorable prognosis (75% 5-year survival). They concluded that type A and B are thought to be in situ peripheral adenocarcinoma, whereas type C was thought to be an advanced stage of types A and B. We focused our attention on this point and retrospectively reviewed 28 BACs without active fibroblastic proliferation. All 28 tumors showed no vessel invasion, and no lymph node or pulmonary metastasis histopathologically. There were two deaths unrelated to cancer, and 26 patients are alive without recurrence. The 5-year survival rate of all patients was 90.1%. Therefore, we conclude that limited pulmonary resection could be a curative operation, an alternative to lobectomy for histologically confirmed BAC without active fibroblastic proliferation [10]. On the basis of this conclusion, we designed a prospective trial to confirm the effectiveness of limited resection for BAC without active fibroblastic proliferation that is confirmed by intraoperative pathologic examination. We began this study in October 1996 with 42 patients enrolled in the study. Of the 42 patients, 36 patients underwent limited resection; however, in 6 patients the procedure needed to be changed to lobectomy because these patients were not eligible for limited resection at intraoperative examination. Limited resection includes wedge resection and segmental resection. We performed wedge resection instead of segmental resection when feasible because we believe that wedge resection could be a curative resection and pulmonary volume should be reserved as much as possible. It was confirmed by intraoperative pathologic examination that the surgical margins were free from cancer. All patients continue to be followed, with a median follow-up period of 30 months. They are all currently alive and free from local or distant recurrence. Because the patient number and the follow-up period is insufficient to reach a definitive conclusion and BAC has a less aggressive nature than other adenocarcinomas [11], further study and long-term follow-up will be necessary to determine whether limited resection can be a curative procedure for BAC without active fibroblastic proliferation. In addition, we believe that it is useful to preserve pulmonary function by means of limited pulmonary
Ann Thorac Surg 2001;71:971– 4
resection, as these patients occasionally have synchronous or metachronous multiple BACs [14]. In conclusion, our early results indicate that limited resection may be an acceptable alternative to lobectomy for small peripheral lung cancers if they are histologically confirmed BAC without active fibroblastic proliferation. We thank Drs Mina Okuizumi and Iwao Emura for their help with the histologic examinations.
References 1. Kaneko M, Eguchi K, Ohmatsu H, et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996;201:798 – 802. 2. Sone S, Takashima S, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351:1242–5. 3. Lung Cancer Study Group (Prepared by Ginsberg RJ, Rubinstein LV). Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615–23. 4. Tsubota N, Ayabe K, Doi O, at al. Ongoing prospective study of segmentectomy for small lung tumors. Ann Thorac Surg 1998;66:1787–90. 5. Takizawa T, Terashima M, Koike T, et al. Lymph node metastasis in small peripheral adenocarcinoma of the lung. J Thorac Cardiovasc Surg 1998;116:276– 80. 6. Konaka C, Ikeda N, Hiyoshi T, et al. Peripheral non-small cell lung cancers 2.0 cm or less in diameter: proposed criteria for limited pulmonary resection based upon clinicopathological presentation. Lung Cancer 1998;21:185–91. 7. Kurokawa K, Matsuno Y, Noguchi M, Mizuno S, Shimosato Y. Surgically curableearlyadenocarcinoma in the periphery of the lung. Am J Surg Pathol 1994;18:431– 8. 8. Shimosato Y, Suzuki A, Hashimoto T, et al. Prognostic implications of fibrotic focus (scar) in small peripheral lung cancers. Am J Surg Pathol 1980;4:365–73. 9. Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung: histologic characteristics and prognosis. Cancer 1995;75:2844–52. 10. Yamato Y, Souma T, Yoshiya K, et al. Feasibility of limited pulmonary resection for bronchiolo-alveolar type adenocarcinoma with minimal fibrotic foci (in Japanese). Haigan (Japanese Journal of Lung Cancer) 1998;38:109–15. 11. Koizumi N, Akita S, Sakai K, et al. Cloudy nodule on HRCT: a new clinico-radiologic entity of pulmonary adenocarcinoma. Radiation Med 1995;13:273– 8. 12. Tsuchida M, Yamato Y, Aoki T, et al. CT-guided agar marking for localization of nonpalpable peripheral pulmonary lesions. Chest 1999;116:139– 43. 13. Warren WH, Faber LP. Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma: five-year survival and patterns of intrathoracic recurrence. J Thorac Cardiovasc Surg 1994;107:1087–94. 14. McElvaney G, Miller RR, Muller NL, et al. Multicentricity of adenocarcinoma of the lung. Chest 1989;95:151– 4.
Background. We reported that bronchioloalveolar adenocarcinoma (BAC) without active fibroblastic proliferation of the lung had no lymph node and pulmonary metastasis and had a favorable prognosis. However, there has been no prospective trial regarding limited pulmonary resection for this type of BAC. The purpose of this study is to confirm the effectiveness of limited resection for histologically confirmed BAC without active fibroblastic proliferation. Methods. From 1996 through 1999, 42 patients who had small peripheral lung tumors (⬉ 20 mm), suspected of being BAC, were enrolled in this trial. The patient population consisted of 24 men and 18 women with a mean age of 58.4 years. Limited resection was completed when BAC, without both active fibroblastic proliferation and lymph node metastasis, was con-
firmed histologically by intraoperative pathologic examination. Results. Limited resection was completed in 36 patients, wedge resection in 34, and segmentectomy in 2 patients. In 6 patients, the procedure was converted into lobectomy because of pathologic invasive sign in 3, active fibroblastic proliferation in 1, and for other reasons in 2 patients. All patients have been followed for a median follow-up period of 30 months and are alive without sign of recurrence. Conclusions. Our early results indicate that limited resection may be an acceptable alternative to lobectomy for histologically confirmed BAC without active fibroblastic proliferation. (Ann Thorac Surg 2001;71:971– 4) © 2001 by The Society of Thoracic Surgeons
I
attention on this point and reviewed 28 patients with BAC with minimal fibrotic foci who underwent lobectomy and systemic lymph node dissection. All of the patients had neither lymph node nor pulmonary metastasis with favorable prognoses [10]. On the basis of these promising results, we performed a prospective study to confirm the effectiveness of limited resection for histologically confirmed BAC without active fibroblastic proliferation.
n recent years in Japan, small peripheral adenocarcinomas of the lung have become more commonly detected by computed tomography (CT) [1, 2]. However, limited pulmonary resection for small peripheral adenocarcinomas remains controversial [3, 4], because it is known that 10% to 20% of small adenocarcinomas of the lung have lymph node involvement or pulmonary metastasis [5–7]. Shimosato and colleagues [8] have demonstrated that the characteristics of the central fibrosis (scar) were probably more important than the size of tumor for estimating the prognosis of patients with peripheral adenocarcinoma of the lung. Noguchi and colleagues [9] grouped small adenocarcinomas of the lung into six types by histologic examination and have reported that type A (localized bronchioloalveolar carcinoma [BAC]) and type B (localized BAC with foci of structural collapse of alveoli) showed the most favorable prognosis of the six types, whereas type C (localized BAC with foci of active fibroblastic proliferation) was thought to be an advanced stage of types A and B. We focused our
Accepted for publication Oct 18, 2000. Address reprint requests to Dr Yamato, Department of Thoracic and Cardiovascular Surgery, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata City, 951-8510 Japan; e-mail: [email protected].
© 2001 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
Material and Methods From October 1996 through August 1999, 42 patients who had small peripheral (situated peripherally beyond subsegmental bronchi) lung tumors of 2 cm or less and were suspected of BAC based on chest CT and by CT-guided lung biopsy were enrolled in a single center trial. Chest CT demonstrated no lymph node metastases, and routine examination revealed no metastatic lesions. The patient population consisted of 24 men and 18 women, with a mean age of 58.4 years (range, 32 to 76 years) at the time of the pulmonary resection. In 39 of the 42 patients, diagnosis of BAC was established preoperatively by CT-guided lung biopsy. Radiologically, this type of BAC is expressed by CT as a clearly demarcated nodular area 0003-4975/01/$20.00 PII S0003-4975(00)02507-8
972
YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
Ann Thorac Surg 2001;71:971– 4
Fig 1. High resolution computed tomography showing a clearly demarcated nodular area of lower density than vessels, so-called ground-glass attenuation.
of lower density than vessels, the so-called ground-glass attenuation (Fig 1) [11]. The tumor diameters measured by chest CT ranged from 6 to 20 mm, with a mean diameter of 13.6 mm. Table 1 summarized the clinical characteristics of these patients. Histopathologically, this type of BAC shows retained alveolar structure and replacement growth pattern of alveolar epithelial cells without active fibroblastic proliferation and invasive sign to the pleura and stroma (Fig 2), which almost corresponds to Noguchi’s classification type A or B [9]. Intraoperative pathologic examination was done using hematoxylin and eosin-stained section from the largest cut surface of the tumor. Postoperative pathologic examinaTable 1. Characteristics of 42 Patients Enrolled in This Study Characteristics
Data
Age (yr) Sex Male Female Preoperative diagnosis Adenocarcinoma Undiagnosed Tumor diameter (mm) measured by Chest CT Resected specimen Surgical procedures Wedge resection Segmental resection Lobectomy Reasons for conversion to lobectomy Pathological invasive sign AFP Multiple lesions in one lobe Nonpalpable lesion
32–76 (58.4) 24 18 39 3 6 –20 (13.6) 4 –25 (12.3) 34 2 6 3 1 1 1
Data are given as range (mean) or number. CT ⫽ computed tomography;
Fig 2. Microscopic findings of bronchioloalveolar adenocarcinoma without active fibroblastic proliferation showing retained alveolar structure and replacement growth pattern of alveolar epithelial cells without active fibroblastic proliferation. (Hematoxylin and eosin stain; A: original magnification, ⫻2; B: original magnification, ⫻160.)
AFP ⫽ active fibroblastic proliferation.
tion was performed using hematoxylin and eosin and elastica van Gieson-stained sections from two or three cut surfaces of the tumor. Wedge resection or segmental resection with hilar and mediastinal lymph nodes sampling (two or three nodes in almost all patients) was performed on these patients through a thoracotomy, followed by intraoperative pathologic examination in all patients. After BAC without both active fibroblastic proliferation and invasive signs with no lymph node metastasis was confirmed histologically, limited resection was completed. If active fibroblastic proliferation, invasive sign, or lymph node metastasis was detected by intraoperative pathologic examination, the surgical procedure was converted into a lobectomy with lymph node dissection (Fig 3). Informed consent was obtained from all patients. Only 1 patient of those who were thought to be eligible for limited resection refused to participate in this study. Patients enrolled in this study have been followed at 3-month intervals after operation. Follow-up evalua-
Ann Thorac Surg 2001;71:971– 4
YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
973
Comment
Fig 3. The study design of limited resection for bronchioloalveolar adenocarcinoma (BAC). (AFP ⫽ active fibroblastic proliferation; CT ⫽ computed tomography.)
tion included blood examination and chest roentgenogram at 3-month intervals, and chest CT at 6-month intervals. The follow-up periods have ranged from 47 to 12 months: 12 to 23 months in 12 patients, 24 to 35 months in 20, and 36 to 47 months in 10 patients. The median follow-up period was 30 months.
Results There were no operative or hospital deaths and no serious complications postoperatively. Limited resection was completed in 36 patients, wedge resection in 34, and segmental resection in 2 patients. In 6 patients, the surgical procedure was converted into lobectomy because of pathologic invasive sign in 3 patients, active fibroblastic proliferation in 1, multiple lesions in one lobe in 1, and nonpalpable lesion in 1 patient. In all patients, there was no metastasis in hilar and mediastinal lymph nodes that were sampled intraoperatively. Postoperative pathologic diagnoses of all tumors were in accord with intraoperative pathologic results. The tumor diameter measured in resected specimens ranged from 4 to 25 mm, with a mean diameter of 12.3 mm. To localize nonpalpable peripheral pulmonary lesions, we have developed a new technique of CT-guided agar marking [12]. Agar was injected through an 18-gauge needle and placed near the target lesion with CT. Agar could be detected as a hard nodule by manual palpation, and the lesion was resected during thoracotomy. Sixteen of the 42 patients required agar marking preoperatively to localize and resect nonpalpable tumors. All patients have been followed to date and are alive without a sign of local or distant recurrence.
In recent years, small peripheral adenocarcinomas of the lung have been more commonly detected in Japan as a result of recent advances in diagnostic radiology and lung cancer screening programs using chest CT [1, 2]. Even for these small tumors, lobectomy with lymph node dissection is commonly performed in Japan, because it is known that 10% to 20% of small peripheral adenocarcinomas of the lung constitutes progressive disease. Takizawa and colleagues [5] demonstrated that 17% of small (⬍ 2 cm) peripheral adenocarcinomas had lymph node metastases and concluded that lobectomy and hilar/mediastinal lymphadenectomy are required even in such cases. Konaka and colleagues [6] similarly analyzed patients with peripheral lung cancers of 2.0 cm or less in diameter having undergone surgical resection and demonstrated that 17.5% of all patients had lymph node involvement. For these reasons, the indication of limited pulmonary resection for small peripheral adenocarcinomas remains controversial and has not been clearly established. There have been several studies concerning limited resection for small peripheral lung cancer. The Lung Cancer Study Group (Ginsberg and Rubinstein) [3] reported a prospective randomized trial comparing limited resection with lobectomy for patients with peripheral T1N0 non-small cell lung cancer and concluded that lobectomy must still be considered the surgical procedure of choice for patients with these tumors. On the other hand, Warren and Faber [13] reviewed, retrospectively, patients with stage I non-small cell lung cancer having undergone either segmental resection or lobectomy and the results revealed that there was a very high loco/regional recurrence rate in the segmentectomy group, however, no significant difference in survival rates between patients with tumors 3.0 cm or smaller in diameter undergoing lobectomy and patients undergoing segmentectomy. Considering the results of these studies, we believe that it is not only the size but also the histologic characteristics of tumors that need to be considered to determine the indication of limited resection for small peripheral lung cancers. However, reports documenting the indication of limited pulmonary resection for small peripheral lung cancers also taking into account the histologic type have been scarce. Shimosato and colleagues [8] reexamined peripheral lung cancers of less than 3 cm in diameter histologically and stated that the degree of collagenization or hyalinization might indicate the relative length of time between the tumor development and its surgical removal. They revealed that in adenocarcinoma with increased collagenization or hyalinization in the fibrotic focus, the degree of pleural invasion and incidence of lymph node metastasis and blood vessel invasion were greater and thus the prognosis of the patient was poorer than in cases with no or slight collagenization, and concluded that the characteristics of the central fibrosis (scar) were probably more important than tumor size for estimating the prognosis of patients with peripheral adenocarcinoma of less than 3 cm in diameter. Noguchi and colleagues [9] have
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YAMATO ET AL LIMITED RESECTION FOR SMALL ADENOCARCINOMA
reported that they grouped small adenocarcinomas of the lung into six types by histologic examination, and type A (localized BAC) and type B (localized BAC with foci of structural collapse of alveoli) showed no lymph node metastasis, rare vascular and pleural invasion, and the most favorable prognosis (100% 5-year survival) of the six types, whereas type C (localized BAC with foci of active fibroblastic proliferation) showed a less favorable prognosis (75% 5-year survival). They concluded that type A and B are thought to be in situ peripheral adenocarcinoma, whereas type C was thought to be an advanced stage of types A and B. We focused our attention on this point and retrospectively reviewed 28 BACs without active fibroblastic proliferation. All 28 tumors showed no vessel invasion, and no lymph node or pulmonary metastasis histopathologically. There were two deaths unrelated to cancer, and 26 patients are alive without recurrence. The 5-year survival rate of all patients was 90.1%. Therefore, we conclude that limited pulmonary resection could be a curative operation, an alternative to lobectomy for histologically confirmed BAC without active fibroblastic proliferation [10]. On the basis of this conclusion, we designed a prospective trial to confirm the effectiveness of limited resection for BAC without active fibroblastic proliferation that is confirmed by intraoperative pathologic examination. We began this study in October 1996 with 42 patients enrolled in the study. Of the 42 patients, 36 patients underwent limited resection; however, in 6 patients the procedure needed to be changed to lobectomy because these patients were not eligible for limited resection at intraoperative examination. Limited resection includes wedge resection and segmental resection. We performed wedge resection instead of segmental resection when feasible because we believe that wedge resection could be a curative resection and pulmonary volume should be reserved as much as possible. It was confirmed by intraoperative pathologic examination that the surgical margins were free from cancer. All patients continue to be followed, with a median follow-up period of 30 months. They are all currently alive and free from local or distant recurrence. Because the patient number and the follow-up period is insufficient to reach a definitive conclusion and BAC has a less aggressive nature than other adenocarcinomas [11], further study and long-term follow-up will be necessary to determine whether limited resection can be a curative procedure for BAC without active fibroblastic proliferation. In addition, we believe that it is useful to preserve pulmonary function by means of limited pulmonary
Ann Thorac Surg 2001;71:971– 4
resection, as these patients occasionally have synchronous or metachronous multiple BACs [14]. In conclusion, our early results indicate that limited resection may be an acceptable alternative to lobectomy for small peripheral lung cancers if they are histologically confirmed BAC without active fibroblastic proliferation. We thank Drs Mina Okuizumi and Iwao Emura for their help with the histologic examinations.
References 1. Kaneko M, Eguchi K, Ohmatsu H, et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996;201:798 – 802. 2. Sone S, Takashima S, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351:1242–5. 3. Lung Cancer Study Group (Prepared by Ginsberg RJ, Rubinstein LV). Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615–23. 4. Tsubota N, Ayabe K, Doi O, at al. Ongoing prospective study of segmentectomy for small lung tumors. Ann Thorac Surg 1998;66:1787–90. 5. Takizawa T, Terashima M, Koike T, et al. Lymph node metastasis in small peripheral adenocarcinoma of the lung. J Thorac Cardiovasc Surg 1998;116:276– 80. 6. Konaka C, Ikeda N, Hiyoshi T, et al. Peripheral non-small cell lung cancers 2.0 cm or less in diameter: proposed criteria for limited pulmonary resection based upon clinicopathological presentation. Lung Cancer 1998;21:185–91. 7. Kurokawa K, Matsuno Y, Noguchi M, Mizuno S, Shimosato Y. Surgically curableearlyadenocarcinoma in the periphery of the lung. Am J Surg Pathol 1994;18:431– 8. 8. Shimosato Y, Suzuki A, Hashimoto T, et al. Prognostic implications of fibrotic focus (scar) in small peripheral lung cancers. Am J Surg Pathol 1980;4:365–73. 9. Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung: histologic characteristics and prognosis. Cancer 1995;75:2844–52. 10. Yamato Y, Souma T, Yoshiya K, et al. Feasibility of limited pulmonary resection for bronchiolo-alveolar type adenocarcinoma with minimal fibrotic foci (in Japanese). Haigan (Japanese Journal of Lung Cancer) 1998;38:109–15. 11. Koizumi N, Akita S, Sakai K, et al. Cloudy nodule on HRCT: a new clinico-radiologic entity of pulmonary adenocarcinoma. Radiation Med 1995;13:273– 8. 12. Tsuchida M, Yamato Y, Aoki T, et al. CT-guided agar marking for localization of nonpalpable peripheral pulmonary lesions. Chest 1999;116:139– 43. 13. Warren WH, Faber LP. Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma: five-year survival and patterns of intrathoracic recurrence. J Thorac Cardiovasc Surg 1994;107:1087–94. 14. McElvaney G, Miller RR, Muller NL, et al. Multicentricity of adenocarcinoma of the lung. Chest 1989;95:151– 4.